Cryotreatment device and method

ABSTRACT

Devices and methods for cooling vessel walls to inhibit restenosis in conjunction with medical procedures such as coronary artery angioplasty. Stenosed vessel walls can be cooled prior to angioplasty, after angioplasty, or both. The invention is believed to inhibit restenosis through cooling to a temperature near freezing, preferably without causing substantial vessel wall cell death. One catheter device includes a distal tube region having coolant delivery holes radially and longitudinally distributed along the distal region. In some devices, holes spray coolant directly onto the vessel walls, with the coolant absorbed into the blood stream. In other embodiments, a balloon or envelope is interposed between the coolant and the vessel walls and the coolant returned out of the catheter through a coolant return lumen. Some direct spray devices include an occlusion device to restrict blood flow past the region being cooled. Pressure, temperature, and ultrasonic probes are included in some cooling catheters. Pressure control valves are included in some devices to regulate balloon interior pressure within acceptable limits. In applications using liquid carbon dioxide as coolant, the balloon interior pressure can be maintained above the triple point of carbon dioxide to inhibit dry ice formation. Some cooling catheters are coiled perfusion catheters supporting longer cooling periods by allowing perfusing blood flow simultaneously with vessel wall cooling. One coiled catheter is biased to assume a coiled shape when unconstrained and can be introduced into the body in a relatively straight shape, having a stiffening wire inserted through the coil strands.

CROSS REFERENCE TO RELATED APPLICATIONS

The present application is a continuation of co-pending U.S. applicationSer. No. 11/734,762, filed Apr. 12, 2007; which is a divisional of andclaims the benefit under 35 U.S.C. §121 of U.S. patent application Ser.No. 09/625,163, filed Jul. 25, 2000, now U.S. Pat. No. 7,220,257; whichis related to U.S. patent application Ser. No. 09/229,080, filed Jan.12, 1999, now U.S. Pat. No. 6,290,696; which is a divisional of U.S.patent application Ser. No. 08/812,804, filed Mar. 6, 1997, now U.S.Pat. No. 5,868,735; the entire disclosures of which are all incorporatedherein by reference.

FIELD OF THE INVENTION

The present invention is related generally to medical devices andmethods. More specifically, the present invention relates to devices andmethods for cooling internal body locations. The present inventionincludes methods for cooling stenosed blood vessel regions prior to andsubsequent lo angioplasty to inhibit restenosis.

BACKGROUND OF THE INVENTION

Conventional angioplasty has been performed for several decades,prolonging the lives of an ever-increasing number of patients.Angioplasty procedures involve the dilatation of a balloon placed acrossa lesion in a coronary artery. Dilatation of the balloon in turn dilatesthe lesion, opening the artery for increased blood flow. In some cases,however, the goal of the angioplasty procedure is, in whole or in part,frustrated by complete or partial reclosure of the artery at the lesion.Two mechanisms are believed to be principally responsible for reclosureof the artery, these are restenosis and recoil. Restenosis is believedto be caused by continued growth or regrowth of the smooth muscle cellsassociated with the lesion. Recoil is in part a mechanical processinvolving elastic rebound of the dilated lesion.

Several means have been disclosed for addressing the problem ofrestenosis. These include, among others, radiation treatments to slow orprevent smooth muscle cell proliferation associated with the restenoticprocess. Certain drug therapies have been proposed to prevent or slowrestenosis.

Several means have also been developed to address the issue of recoil.One of the more significant developments in this area has been stents,which can be permanently deployed to mechanically hold open lesions.Although stents have been found to be highly effective, they mayirritate the wall of an artery in which they are implanted. Some believethat this may encourage limited restenosis. Warming of the lesion duringdilatation has also been disclosed to prevent or slow recoil. Warmingthe lesion is believed to soften the lesions such that it may be“remodeled” that is, thinned under low pressure. Heating of the lesion,however, is believed to cause an injury response which may cause somerestenosis.

What would be desirable and advantageous is a method and apparatus forreducing the likelihood of restenosis.

SUMMARY OF THE INVENTION

The present invention includes devices and methods for reducing adversereactions to medical procedures impacting body vessels such as bloodvessels by cooling the effected vessel regions. The invention includesmethods and devices for cooling blood vessel sites having a lesion whichare to be impacted by angioplasty. The vessel wall cooling can beperformed before, during, and/or after the angioplasty procedure and anycombinations thereof. The cooling is believed to lessen any injuryresponse which may be caused by the angioplasty, as the body mayinterpret the angioplasty procedure as an injury and react in ways thatcan cause restenosis.

One set of methods according to the present invention include distallyadvancing a tubular catheter having numerous radially outwardly pointingcoolant distributing orifices supplied by a coolant lumen in fluidcommunication with a proximal coolant source. The coolant can be sprayedin the direction of the vessel wall and toward the lesion. One deviceused includes an expandable occlusion device for expanding against thevessel walls and greatly reducing, if not stopping, blood flow duringthe procedure. Occluding the blood vessel can reduce the vessel wallwarming which is caused by blood flow through the vessel. Occluding thevessel also lessens the removal of coolant by the flowing blood.Occluding devices can be disposed on the cooling catheter shaftproximally and/or distally of the coolant distributing orifices.Inflatable occluding devices can be inflated by either the coolant fluidor by an inflation fluid other than the coolant. The coolant can beliquid, gas, or liquid that changes phase to gas during the coolingprocess.

One device for cooling a length of body vessel interior includes meansfor distributing coolant at multiple locations over the vessel interior.The device can also have a coolant delivery shaft having a first lumencoupled to tire coolant distribution means. Some devices also have meansfor occluding the body vessel interior, for example, an inflatableoccluding element. One embodiment uses the coolant as an inflationfluid. Some embodiments include a second lumen for inflating theoccluding element. One group of embodiments utilizes an inflatableballoon or skirt. In general, the cooling catheter can include a distalregion for radially and longitudinally distributing coolantsimultaneously over the target vessel region. The infused coolant can beabsorbed into the blood and carried downstream. In some methods, thecooling catheter distal region includes pressure and/or temperaturesensors coupled to external readouts for following the progress of theprocedure. One method utilizes an ultrasonic transducer disposed in thecatheter distal region for determining freeze status of the lesion orvessel walls. In one method, an ultrasonic transmitter is disposedwithin the vessel which can be monitored by a receiver outside the body.In another embodiment, an ultrasonic receiver is disposed within thevessel, which receives externally generated ultrasound. The attenuationof sound by the vessel walls and any lesion is less for frozen tissuethan for unfrozen tissue. In one method, the internal pressure of thevessel is measured and followed to maintain the pressure in the vesselwithin specified limits.

One device used according to the present invention includes an envelopeor inflatable balloon disposed between the coolant distributor and theblood vessel wall. In this embodiment, the coolant does not contact thelesion directly but cools the lesion through the balloon envelope wall.One embodiment of this device can radially and longitudinally distributecoolant over the length of vessel inside the balloon with a rolatableand axially slidable coolant distributing probe which can have a distalbend or curve with a distal most delivery orifice. The slidable androtatable coolant delivery tube can be aimed at different locations atdifferent times to cover whatever target sites are desired. Using thisembodiment, one side of the vessel wall can be targeted for coolingwhile an opposing or adjacent site left uncooled or less cooled. Thecatheter can include pressure and temperature sensors inside the balloonas well as an ultrasonic transducer. Some embodiments include guide wiretubes through the balloon while other embodiments have fixed wiresextending through the balloon. Some embodiments utilize a liquid coolantwhile others utilize a coolant which vaporizes from liquid to gas insidethe balloon.

Coolant can exit the balloon interior through an exhaust or returnopening extending from the balloon interior. In some embodiments, theexhaust port exits from the balloon interior and into the blood stream.In other embodiments, the return port leads to a return lumen extendingproximally through the catheter shaft. Some embodiments have a pressurecontrol valve in fluid communication with the balloon interior tomaintain the balloon pressure above a minimum, below a maximum, or both.In some embodiments, a pressure control valve is disposed near theproximal end of the catheter shaft in communication with a coolantreturn lumen. A pressure control valve can be used in conjunction withliquid carbon dioxide as a coolant to maintain the pressure inside theballoon above the triple point of carbon dioxide to inhibit dry iceformation when the liquid carbon dioxide vaporizes.

Catheters according to the present invention can include alongitudinally and radially spraying coolant distributor having multipledistributor tubes feed off a common manifold. In one embodiment, themultiple tubes have varying lengths and have outwardly directed sprayorifices disposed near the tube ends. The multiple tubes can thus covervarious angular sectors and can cover the length of the distributor LOinclude a vessel interior region. Some embodiments are used directlywithin a vessel interior while other embodiments are used within aballoon or envelope interposed between the distributor and the vesselwalls. Another coolant distributor embodiment includes a longitudinallydisposed tube having numerous holes through the tube wall into a coolantlumen within. In one embodiment, the holes are visible with the unaidedeye while another embodiment has micropores not individually viewablewith the unaided eye.

One cooling balloon catheter includes a pressure-regulating valvedisposed between a coolant supply tube and the balloon interior. Whenthe coolant supply tube pressure exceeds a pressure level, the valve canopen and release coolant into the balloon interior, in one embodiment,the valve includes a cap covering the coolant tube distal end which isbiased shut by a spring. In one catheter, the valve is slidinglydisposed over a guide wire tube. One coolant-distributing deviceincludes an elongate tube having a coolant lumen and a control rod orcontrol wire therethrough. The control rod or wire can be operablyconnected to a distal spring-loaded valve, with the spring disposedwherever practicable on the device. The distal valve can be opened awayfrom a valve seat allowing coolant to escape from the tube. In someembodiments, the distal valve is shaped to spray radially outward towardthe vessel interior walls.

Catheters incorporating the present invention can include warmingjackets to lessen unwanted cooling by catheter regions proximal of thedistal cooling region. The warming jacket can include a substantiallyannular warming fluid supply lumen as well as an optional warming fluidreturn lumen. In some embodiments, saline is used as the warming fluidand is vented out the catheter distal end into the blood stream. Thewarming fluid can reduce the cooling caused by the coolant lumen orlumens disposed in the catheter shaft.

Perfusion cooling catheters are also within the scope of the presentinvention. Perfusion cooling catheters can provide for prolonged coolingof the vessel walls by including a perfusion pathway to allow blood flowpast or through the distal cooling end of the catheter. One embodimentincludes a helical coil supplied with coolant through a coolant lumendisposed in a longitudinal shaft. Perfusing blood flow is allowedthrough the lumen passing through the coil center. Another embodimentincludes a radially expandable helical coil. One expandable helical coilis biased to assume a coiled configuration when unconstrained. Thecoiled can be substantially straightened by a stiffening member or wireinserted through the coil. The relatively straightened coil can beinserted through the vasculature to the site to be cooled. Once at thesite, the stiffening wire can be retracted, allowing the unconstrainedcoil portion to assume the coil shape. One embodiment includes only asingle turn coil while other embodiments include multiple turn coils.One perfusion catheter has a pressure reducing orifice near the coolingregion inlet to provide cooling through a pressure drop. This cathetercan be used in conjunction with a vaporizing coolant such as liquidcarbon dioxide to provide a cold distal cooling region. One embodimentincludes a fluid block near the coil outlet which can serve to block thereturn of liquid coolant in a liquid to gas, vaporizing cooling coil.

One cooling catheter is a catheter selected to be undersized relative tothe vessel region to be cooled. The undersized catheter can cool thevessel walls without directly contacting the walls with the coolingballoon. The cooling balloon can include cooling balloons previouslydiscussed, and having an outside diameter less than the inside diameterof the vessel region to be cooled. One end of the balloon, such as theproximal end, can include a radially expandable skirt which can serve toboth occlude blood flow and to center one end of the balloon. The skirtcan stop or greatly reduce blood flow between the balloon outer wallsand the vessel inner walls. The quiescent volume of blood can be cooledby the balloon, with the blood volume in turn cooling the vessel walls.This design allows vessel wall cooling without substantial directcontact by a cold balloon wall. It may be desirable in some applicationsto minimize direct contact between an extremely cold balloon and avessel wall. Some embodiments include both a proximal and a distalexpandable skirt, which can provide improved centering and betterisolation of a blood volume to be cooled. Some embodiments utilizeskirts inflated by the coolant and having an inflatable outer ring. Someembodiment expandable skirts are expanded using an inflation fluiddifferent than the coolant.

In use, the present invention can be used to cool a stenosed vesselregion that is about to be dilated with angioplasty, is being dilated,or already has been dilated. The cooling preferably does not freeze thevessel cell walls sufficient to cause substantial cell death.

In use, the present invention can also be used to freeze tissue, causingtissue necrosis, for example, to treat arrhythmias. Tissue sites includetissue of the heart chamber walls and a suitably targeted interior wallof a pulmonary vein. In some such applications coolant is directlysprayed onto the tissue to be cryoablated. The direct spray can bedirected in many directions about the coolant delivery tube or directedprimarily in one direction. In other applications coolant is sprayedtoward the tissue to be frozen, with a balloon envelope interposedbetween the coolant and the tissue. Cryoablation can be accomplishedwith perfusion cooling balloons and with cooling devices havinginflatable occlusion balloons or skirls.

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1 is a fragmentary, longitudinal cross-sectional view of a stenosedvessel region having a catheter occluding the vessel and distributingcoolant onto or near the stenosis;

FIG. 2 is a fragmentary, longitudinal cross-sectional view of a catheterhaving an axially and radially moveable coolant distributing tube andinstrument probe disposed within an inflatable balloon;

FIG. 3 is a fragmentary, longitudinal cross-sectional view of a fixedwire catheter having an axially and radially moveable coolantdistributing tube and sensors disposed within an inflatable balloondisposed within a stenosed vessel;

FIG. 4 is a fragmentary, cut-away, perspective view of a catheter havinga coolant distributor including multiple distributor tubes of varyinglengths disposed within a balloon;

FIG. 5 is a fragmentary, perspective view of the coolant distributor ofFIG. 4;

FIG. 6 is a fragmentary, cutaway, perspective view of a cooling catheterhaving a porous coolant distributor;

FIG. 7 is a fragmentary, longitudinal, cross-sectional view of a coolingcatheter having a spring-loaded pressure relief valve coolantdistributor;

FIG. 8 is a longitudinal, cross-sectional view of a coolant deliverycatheter having a proximal spring loaded control handle coupled to adistal valve;

FIG. 9 is a fragmentary, cross-sectional view of a cooling cathetershaft region having a warming jacket;

FIG. 10 is a transverse cross-sectional view taken along plane 10-10 ofFIG. 9;

FIG. 11 is a fragmentary, perspective view of a cooling coil which canbe used in a perfusion cooling catheter;

FIG. 12 is a fragmentary, perspective view of a coiling having an inflowpressure reducing orifice and an outflow fluid block which can be usedin a perfusion cooling catheter having a liquid to gas phase change;

FIG. 13 is a fragmentary, longitudinal cross-sectional view of a coil,perfusion, cooling catheter in a straight configuration constrained byan inserted guide wire;

FIG. 14 is a fragmentary, perspective view of the cooling catheter ofFIG. 13 is an unconstrained, coiled configuration within a vessel; and

FIG. 15 is a fragmentary, perspective view of an occluding coolingballoon catheter disposed in a vessel and smaller in profile than thevessel region being cooled.

DETAILED DESCRIPTION OF THE INVENTION

FIG. 1 illustrates a vessel cooling device 30 disposed within a bodyblood vessel 32 having a vessel wall 34, a lumen 38 therethrough, and astenosis, lesion, or plaque 36 partially occluding the vessel lumen andextending over a length of vessel. In the embodiment illustrated,cooling device 3 u includes a tubular shaft 48 having a proximal region46, distal region 40, a distal end 42, and a distal tip 44. Shaft 48includes a coolant tube 50 having a lumen therethrough and a pluralityof coolant delivery orifices 52 disposed longitudinally and radiallyabout the shaft distal region. The coolant is illustrated as sprayingdirectly on the lesion. Cooling device 30 also includes an occlusiondevice 55 for occluding the vessel lumen. In the embodiment illustrated,an annular exhaust lumen 43 is defined between coolant tube 50 and acoaxially disposed exhaust tube 45. Exhaust tube 45 can be used toremove coolant from the vessel, in either liquid or gaseous form. Inthis embodiment, an annular inflation lumen 53 for expanding occlusiondevice 55 is defined between exhaust tube 45 and a coaxially disposedinflation tube 57. Cooling device 30 is illustrated having proximalregion 46 extending out of the body to a coolant supply 56, and aninflation fluid supply 58. In the embodiment illustrated in FIG. 1,occlusion device 55 includes an inflatable balloon having a ballooninterior 54. In the embodiment illustrated, balloon 55 is inflated withan inflation fluid different than the coolant fluid. In otherembodiments, the occlusion device is inflated or expanded using thecoolant fluid itself. In some embodiments, the coolant is supplied as aliquid which vaporizes into a gas and the gas inflates the occlusiondevice. Coolant supply 56 and inflation fluid supply 58 are illustratedjoining to shaft proximal region 46 at a manifold 60.

Coolant supply 56 can provide a variety of coolants, depending on theembodiment of the invention elected. In some embodiments, a liquidcoolant such as saline, nitrous oxide or ethyl alcohol is used. In otherembodiments, a liquid coolant is used that can vaporize to a gas uponapplication. Liquid coolants that can vaporize to a gas and providecooling include CO, nitrogen, liquid nitrous oxide, Freon, CFC's, HFC's,and other noble gasses

In the embodiment illustrated in FIG. 1, the coolant is sprayed directlyonto the stenosis. Orifices 52 distribute the coolant bothlongitudinally over a length of the shaft and radially about the shaft,using coolant distribution simultaneously through multiple orifices.Occlusion device 54, when used, can serve to enhance the cooling effectby blocking or greatly inhibiting blood flow which can warm the area tobe cooled. In embodiments utilizing coolants which vaporize upondelivery, the vessel lumen may contain a moderate amount of gas, whichcan be absorbed by the body as long as the amount is maintained below asafe limit. In some methods, the gas can displace a large amount ofblood, forcing some blood further downstream. In some embodiments, thecatheter shaft includes a pressure sensor for measuring the internalpressure of the blood vessel for external readout.

In another use of cooling devices according to the present invention,cooling device 30 can be used to ablate or cause tissue necrosis throughtissue freezing, for example within a chamber of the heart or within apulmonary artery. Tissue may be ablated for various reasons, with thetreatment of cardiac arrhythmias being a primary goal of one suchtreatment. In such applications, the cooling is continued for a time andtemperature sufficient to cause cell death. In one such application,similar to the method illustrated in FIG. 1, the coolant is sprayeddirectly onto the tissue to be ablated. Cooling device 30 and subsequentcooling devices discussed are believed to be suitable for causing tissuenecrosis as well as inhibiting restenosis through cooling. In oneapplication, a circumferential region is ablated at a location where apulmonary vein extends from a posterior left atrial wall of a leftatrium in a patient. In one method, tissue is cooled to about 40 degreesCentigrade for a time period greater than about 3 minutes. Tissueablation to treat arrhythmia is well known to those skilled in the art.See, for example, U.S. Pat. Nos. 5,147,355 and 6,024,740, hereinincorporated by reference.

Referring now to FIG. 2, another cooling device 70 is illustrated,having a distal region 72 and a distal end 74. Cooling device 70includes a longitudinally and radially moveable coolant directing tube80 having a lumen 81 and terminating in a coolant orifice 82. A balloonenvelope 76 is interposed between coolant orifice 82 and any vesselstenosis on the vessel interior walls. Balloon envelope 76 defines aballoon interior 78 in device 70. In some embodiments, an instrumentprobe 84 having a pressure sensor 86 and an ultrasonic transducer 88 isdisposed within the balloon. On some embodiments the coolant andinstrument shaft are independently moveable while in other embodiments,the two shafts move longitudinally and rotationally together. In someembodiments, the instrument devices are mounted on the same shaft usedto deliver the coolant. One advantage of moving the coolant deliverytube and instruments together is the position of the coolant tube can berepresented by the position of the instrument. Ultrasonic signalstransmitted by ultrasonic transducer 88 can be picked up by externalmonitoring devices to determine the location of the probe, the extent ofthe stenosis, and, while cooling, the extent of the cooling, as thestenosis, if frozen, can show up distinctively on ultrasound images.Cooling device 70 utilizes longitudinal and rotational movement ofcoolant delivery orifice 82 to distribute coolant at the desiredlocations within the vessel interior. The balloon envelope separates thecoolant from the vessel interior wall but allows cooling of the vesselinterior by the directed coolant delivery, as the balloon envelope canreadily transmit heat. Device 70 illustrates an over-the-wire ballooncatheter having the guide wire removed. In some embodiments, the guidewire is removed from a shaft lumen which is then used to guide thecoolant delivery tube to position inside the balloon. Some embodimentsutilize the coolant to inflate the balloon while other embodimentsutilize a separate inflation fluid. Some embodiments have the ballooninterior pressure controlled by a pressure regulating valve allowingfluid out of the balloon interior only when the fluid has reached asufficiently high pressure, In one embodiment, this valve is locatednear the balloon distal tip, allowing fluid exhaust into the bloodstream. In another embodiment, this valve is disposed as the proximalend of an exhaust lumen extending through the catheter shaft.

Utilizing a rotationally and longitudinally moveable coolant deliveryorifice allows the coolant to be delivered to spot locations along thevessel wall. In particular, lesions on only one side of the vessel canbe isolated and cooled more than the opposing vessel wall. Cooling onlythe desired location can provide the desired degree of cooling in thelocation of the lesion without possibly overcooling vessel walllocations having no lesion present. In another use, device 70 can beused to cryoablate tissue in a pulmonary artery or within the heart.

Referring now to FIG. 3, a cooling device 100 is illustrated in a fixedwire embodiment, having balloon envelope 76, balloon interior 78, and alongitudinal stiffening wire 102 disposed through the balloon. Coolingdevice 100 includes pressure sensor 86 and a temperature sensor 99disposed on wire 102. Ultrasonic device 88 is disposed on a distallybent or curved coolant delivery tube 108. Coolant delivery tube 108terminates in a coolant delivery distal orifice 110, shown directedtoward a stenosis 106 lying along one wall of vessel 32. As illustrated,balloon envelope 76 can lie against stenosis 106, largely precludingwarming blood flow between the balloon and vessel wall. The embodimentillustrated in FIG. 3 also includes a coolant exhaust lumen 112,providing an exhaust route for coolant leaving the balloon. In someembodiments, the exhaust lumen includes a pressure-regulating valve tomaintain the balloon interior pressure above a minimum. Cooling device100 can also be used to cryoablate tissue in a pulmonary artery orwithin the heart, as previously discussed.

Referring now to FIG. 4, a cooling device 120 is illustrated, having ashaft 124 including a coolant supply tube 126 feeding a plurality ofcoolant distribution tubes 128 terminating near radially outwardlydirected coolant delivery orifices or nozzles 130. Orifices 130 areillustrated establishing a spray pattern 123 against or in the directionof balloon envelope 76. Device 120 also includes an annular coolantreturn lumen 132 for allowing spent coolant to exit the balloon. FIG. 5illustrates the coolant distributors in farther detail, showing coolantsupply tube 126 feeding coolant distributor tubes 128 which feedorifices 130. As illustrated, cooling device 120 distributes coolantlongitudinally over a length of balloon and also radially distributescoolant within the balloon interior. In some embodiments, coolantdistributor tubes 128 have orifices 130 oriented toward the same radialdirection, and this radial direction of vessel interior wall can beselected for cooling by rotating coolant supply tube 126. Coolantdistribution tubes 128 can be formed of suitable materials including,for example, Nitinol. Cryoablation of tissue in a pulmonary artery orwithin the heart is also possible using cooling device 120.

Referring now to FIG. 6, another cooling device 140 is illustrated,having generally a shaft 142 including a coolant supply tube 144extending distally into a porous coolant distributor region 146 whichcan be formed as illustrated as a plurality of pores 147 extendingthrough the tube walls. Cooling device 140 also includes a guide wiretube 148 having a guide wire lumen 150 extending therethrough. Porousregion 146 has a distal end 152 which can be sealed tightly to guidewire tube 148 to prevent fluid from exiting through the porous regiondistal end. Device 140 can be used to deliver a liquid coolant which isdelivered through the pores as a gas. the heat of vaporization beingused to provide cooling. The gaseous coolant can serve to inflateballoon envelope 76, and, in the embodiment shown, exits ballooninterior 78 through an annular exhaust or return lumen 154 which isdisposed within shaft 142. In one embodiment delivering CO?, the exhaustlumen is terminated proximally by a pressure-regulating valve whichserves to maintain the pressure of the balloon interior to at least thetriple point of the CO2, to inhibit dry ice formation. In someembodiments, the coolant deliver}' pores are easily visible with thenaked eye, having a nominal diameter of about 0.002 inches to 0.009inches. In other embodiments, the pores are micropores, having a nominaldiameter of about 10 microns to 50 microns. The pores distributed overthe balloon length serve to distribute coolant over the length of theballoon interior. The coolant in the embodiment illustrated also servesto inflate the balloon against the vessel walls. In one application,cooling device 140 can be used to freeze tissue in a pulmonary artery orwithin the heart.

Referring now to FIG. 7, another embodiment of the invention isillustrated in a cooling device 160 having a proximal region 162 and adistal region 164. Device 160 includes a guide wire tube 166 extendingthrough balloon 76 and terminating in an orifice 167. A coolant deliverytube 170 extends midway through balloon interior 78, having an annularcoolant delivery lumen 178 therethrough, bounded by coolant deliverytube 170 and guide wire tube 166, Coolant delivery tube 170 is capped bya pressure relief type valve 172 which is urged proximally againstcoolant delivery tube 170 by a spring 168. Pressure relief valve 172includes a proximal portion 180 adapted to sealingly fit over coolantsupply tube 170 and a distal portion 182 dimensioned to slide over andseal against guide wire tube 166. Coolant device 160 can be used toeither inhibit restenosis through tissue cooling or to treat arrhythmiasthrough tissue ablation with a pulmonary artery or within the heart.

Coolant is illustrated escaping from coolant delivery tube 170 at 174into the balloon interior. Pressure relief valve 172 can be used inconjunction with a coolant undergoing a phase transformation from liquidto gas, such as liquid carbon dioxide. When the liquid coolant in thesupply tube is warmed and attains a pressure exceeding the valve springpressure, valve 172 slides distally, allowing the escape of coolant,typically in a gaseous form, into the balloon interior. Coolant can exitthe balloon interior through a return or exhaust lumen 176, and canultimately exit the proximal end of the catheter shaft. The exhaustlumen can be pressure regulated as well, to maintain a minimum pressurein the balloon interior.

Referring now to FIG. 8, another cooling device 190 is illustrated,having a distal region 192 and a proximal region 194. Cooling device 190includes a coolant delivery tube 196 having a coolant delivery lumen 198within and terminating in a distal coolant delivery orifice 200. Coolantcan be supplied by a proximal coolant supply tube 212 in fluidcommunication with coolant lumen 198. A control handle assembly 214includes a ring 208 biased proximally by a spring 210 and a controlshaft 202 which extends distally through a seal 218 and lumen 198 tomaintain the position of a valve 204 in tension against a valve seat216. Control handle assembly 214 can be urged proximally to urge coupledvalve 204 distally out of valve seat 216, allowing coolant to escape.

In use, distal orifice 200 can be disposed near a region to be cooled orcryoablated, followed by opening valve 204 and releasing coolant intothe vessel region to be cooled or cryoablated. In some embodiments,valve control shaft 202 is a control wire incapable of providingsubstantial compression force, and the force to move valve 200 out ofvalve seat 204 is provided by the coolant pressure which can be providedthrough supply tube 212. In one embodiment, a liquid coolant is utilizedwhich vaporizes to gas at the operating temperature and pressure, andthe phase change urges valve 204 out of valve scat 206 whenunconstrained by shaft 202 and ring 208, allowing escape of coolant asindicated at 206. Cooling device 190 can be used to deliver controlleddoses of coolant at target sites without requiring an interposingballoon. Coolant can be distributed longitudinally over time bylongitudinally moving delivery tube 196. In another embodiment, notrequiring illustration, a spring is disposed against and supportedproximally by a fixture to normally urge a valve seat distally against avalve seat. For example, spring 210 could be disposed distally of seal218 and valve 204 could be disposed proximally of valve seat 216. Inthis embodiment, coolant can be released by retracting a control shaftproximally and moving a valve seat proximally from the valve seat. Inthis embodiment, a central shaft can be normally maintained in a stateof compression which is released to open the distal valve and delivercoolant.

Referring now to FIGS. 9 and 10, a cooling device shaft region 230 isillustrated. Shaft region 230 can be located just proximal of a distalcooling portion such as a cooling balloon or coolant distributingportion. Beginning at the center, a guide wire 244 is disposed within aguide wire lumen 234 defined by a guide wire tube 232, A coolant supplylumen 236 is disposed about guide wire tube 232, defined by coolantsupply tube 237, and is surrounded by a coolant return lumen 238,defined by a coolant return tube 239. One advantage of situating thecoolant supply lumen centrally is situating the coolest fluid furthestaway from the warmest fluid, the blood. A warming fluid return lumen 240is disposed about coolant return tube 239, defined by a warming returntube 241, and a warming fluid supply lumen 242 can be disposed aboutwarming fluid return lumen 240 and contained with a warming fluid supplytube 243. In a preferred embodiment, the warming jacket having thewarming fluid supply and return lumens can provide warming to lessenunwanted cooling of the body vessel walls proximal of the target site.Cooling of a coronary artery region may be desired, or the cryoablatingof a pulmonary artery or heart chamber region, but not the cooling orcryoablation of the vessel all the way from the point of entry to thecoronary artery. As some heat transfer from the body to the coolant willoccur proximal of the target site, the entering coolant will normally becooler near the entry point of the catheter than near the target site.In many applications, excessively cooling the vessel walls may beundesirable. In particular, in some applications, while the distalregion of the cooling device may be centered, the remainder of thedevice may be in direct contact with vessel walls.

To reduce the unwanted cooling, the warming fluid can provide a heattransfer layer between the coolant lumens and the vessel walls. Inpractice, the warming fluids may be of substantially less than bodytemperature, as the purpose is to reduce the cooling of the body vesselwalls, not to warm the body vessel walls. The exact warming fluidtemperatures and flow rates will depend on many factors and can beempirically determined by those skilled in the art. In some embodiments,the outermost tube wall material is formed of or coated with a less heatconductive material, to reduce heat transfer from the warm body wallsinto the coolant fluid.

Referring now to FIG. 11, a subassembly perfusing cooling device 260having a coil 266, a distal region 262 and a proximal region 264 isillustrated, which can be used in conjunction with other proximalcatheter shafts and subassemblies well known to those skilled in theart. Coil subassembly 260 includes a coil inflow region 270 and aplurality of coil strands 268 formed in this embodiment from a singlehelical strand having a lumen 271 therethrough. Coolant can flowspirally and distally through the coil strands, returning through acentrally disposed return lube 274 and exiting the cooled regionproximally at outflow region 272. The coil strands are preferablyinflated with coolant under sufficient pressure to press the strandsagainst the surrounding vessel walls, to provide good heat transfer fromthe walls to the coolant. In one embodiment, the coil 266 is enclosed ina jacket or envelope 276 which can aid in maintaining the coil shapeintegrity. The coil shape allows for long term cooling by allowingperfusing blood flow as indicated at 278. By allowing for perfusion, thevessel wall regions can be cooled for long continuous periods. In onemethod, a liquid coolant is used in conjunction with a coil such as coil266. Coil 266 can be formed of materials such as Nitinol, stainlesssteel, polyimide, PET, or other balloon materials. Coil 266 may beparticularly useful for circumferential cryoablation of a pulmonaryartery region.

Referring now to FIG. 12, another cooling device subassembly 290 isillustrated, similar in many respects to cooling device subassembly 260of FIG. 11. A cooling coil 292 includes inflow region 270 and centrallydisposed outflow tube 274. Coil 292 includes a pressure-reducing orifice270 in the proximal region of the coil and a fluid block or filter 296in the distal region of the coil. Orifice 270 can provide a pressuredrop and phase change from liquid to gas to provide enhanced cooling.Fluid block 296 can provide a trap to prevent fluid from entering returntube 274. Orifice 270 and fluid block 296 can provide an improvedcooling coil for use with vaporizable coolants such as liquid carbondioxide or Freon. The liquid can enter at 270 as a liquid and return at272 as a gas. Coil 292 also includes a plurality of attachment points298 for securing the coil to a longitudinal member. Cooling devicesubassembly 290 is believed particularly suitable for perfusion coolingof vessel walls using liquid coolants which are to undergo a phasetransformation to cool the vessel region. Cooling subassembly 290 mayalso be particularly useful for circumferential cryoablation ofpulmonary artery regions.

Referring now to FIG. 13, a cooling catheter 310 is illustrated, havinga balloon 316 extending from a proximal region 314 to a distal region312 and having a proximal end 315 and a distal end 313. Balloon 316includes a balloon envelope 320 defining a balloon interior 322. Balloon316 is disposed near the distal region of a catheter shaft 311 having acoolant delivery tube 324 defining a coolant delivery lumen 326 therein.Coolant delivery tube 324 can supply coolant to balloon interior 322through coolant delivery orifices 332. A guide wire or stiffening wiretube 328 is disposed coaxially within coolant tube 324. Guide wire tube328 includes a guide wire lumen 330 therein including a guide wire orstiffening wire 318 disposed within. Balloon envelope 320 can be bondedproximally to coolant tube 324 at 315 and bonded to guide wire tube 328at 313. After entering balloon interior 322, coolant can flow proximallyto a coolant return lumen 336 within a coolant return tube 334.

Cooling device 310 can be biased or preformed to assume a coiled shapewhen unconstrained. In FIG. 13, guide wire or stiffening element 318extends through the balloon, constraining the balloon and preventing theballoon from fully assuming its coiled unconstrained shape. In someembodiments, a standard guide wire is used to maintain the constrainedballoon shape. In other embodiments, a stiffening member having a distalregion stiffer than the distal region of a standard guide wire isutilized. In a preferred embodiment, the balloon has a higher length todiameter ratio and a properly dimensioned balloon is not capable ofoccluding the vessel when inflated, as would an angioplasty balloon. Inone embodiment, the device is biased to form a coil when unconstrainedby forming coolant tube 324 and/or guide wire tube 328 of a materialhaving a preformed shape which is reverted to when unconstrained. Thedistal tube sections can be formed of shape memory materials includingshape memory polymers or metals, well known to those skilled in the an.

Upon retraction of guide wire 318, balloon 316 can assume the coil shapeillustrated in FIG. 14. In the embodiments of FIG. 14, balloon 316 formsa single coil capable of cooling or cryoablating a short region ofvessel 32. Device 310 can be used to cool vessel wall regions whileallowing for perfusing blood flow through the coil center. In otherembodiments, multiple coils are formed, allowing for the cooling oflonger vessel wail regions. In use, device 310 can be advanced over aguide wire to a site to be cooled. Once in position near a region thathas been dilated or is to be dilated, guide wire 318 can be retracted,allowing the balloon to form a coil. Either before or after the coilformation, coolant can be injected into the coolant lumen, allowingcoolant to enter balloon interior 322. With the balloon disposed near oragainst the vessel walls, the vessel walls can be cooled or cryoablatedwhile allowing perfusing blood to flow through the coil center. Aftersufficient cooling has occurred, coolant inflow can be stopped, andguide wire 318 can be re-inserted through guide wire lumen 330,imparting a straighter shape to the balloon. Cooling device 310 can beretracted from the blood vessel in the straighter configuration.

Referring now to FIG. 15, another cooling device 350 is disposed withinblood vessel 32. In some embodiments, device 350 is similar in manyaspects to cooling devices having balloons previously discussed. Coolingdevice 350 is dimensioned to allow cooling of the vessel wall withoutrequiring the cooling balloon to directly contact the vessel wall.Device 350 has a distal region 352, a proximal region 354, and a distaltip 356. A cooling balloon 364 is illustrated and can be similar tocooling balloons previously discussed with respect to other embodiments.Balloon 364 has an outer diameter selected to be less than the insidediameter of vessel 32 in which it is disposed. A proximally disposedoccluding device 358 including an expandable outer rim 370 is secured toballoon 364 through a proximal skirt 366 at a proximal waist 368. Ashaft 362 including guide wire 244 within is illustrated extendingproximally of proximal occluding device 358. Shaft 362 can be similar toshafts previously discussed and can vary with the type of balloon usedin the device. Shaft 362 can include lumens for coolant supply andreturn and lumens for inflation fluid.

By dimensioning the balloon to have a profile less than the vessel crosssection, an annular space 372 remains between balloon 364 and vessel 32.The annular space can contain a relatively quiescent blood volume due tothe occluding effect of occluding device 358. Occluding device 358contacting vessel 32 can block most blood flow past the balloon, leavingan unchanging volume of blood. The cooling provided by balloon 364 cancool this still volume of blood, cooling the blood and thereby coolingthe vessel walls adjacent to the blood. Cooling device 350 can thus coolthe vessel walls and any stenosis without contacting the vessel wallswhich can be advantageous where there is a desire to avoid contactingthe vessel walls directly.

Occluding device 358 can be formed of any suitable expandable device,preferably a reversibly expandable device. In one embodiment, expandableouter rim 370 includes an inflatable outer tubular portion 371 and aninflatable double-walled envelope skirt portion 375 in fluidcommunication with the interior of balloon 364, such that inflatingballoon 364 inflates proximal skirt 366 and outer rim 370 to expandagainst the vessel walls. In one embodiment, the skirt is not itselfinflatable but includes tubular lumen portions for inflating the outerrim. After cooling is complete, in one embodiment, the coolant whichserves as the inflation fluid is withdrawn and the proximal skirtcontracts to a smaller profile configuration. In some methods, a vacuumis pulled on the lumen in fluid communication with the proximal skirt.In another embodiment, after cooling is complete, both coolant and aseparate inflation fluid are withdrawn followed by pulling a vacuum onthe inflation lumen, thereby contracting the proximal skirt evenfurther.

In use, cooling devices according to the present invention can be usedto cool an area having a lesion and/or in close proximity to an areahaving a lesion, where contact with an angioplasty balloon or othervessel dilating device is expected. The cooling devices can be used tocool a vessel area where possible irritation or injury is possibleduring a medical procedure. For example, cooling can be performed in anarea where atherectomy or ablation is to be performed. The cooling canalso be used to lessen any adverse impact of minimally invasive surgicalprocedures including cardiac artery bypass surgery. The cooling can beperformed either before or after the medical procedure or both beforeand after the procedure. The cooling is believed by Applicants to lessenthe post-procedure injury response which can include restenosis in thecase of angioplasty.

The vessel walls are preferably cooled for a temperature and periodsufficient to encourage a positive remodeling response after the medicalprocedure. The cooling is preferably for a temperature and lime not sosevere as to irreversibly harm the vessel walls. In particular, freezingthe vessel walls to the point of causing necrosis is preferably avoided.In one method, the vessel walls are cooled to a temperature of betweenabout 0 degrees C. and about 10 degrees C. for a period of between about1 minute and 15 minutes. In a preferred method, the vessel walls arecooled for a period of between about 5 minutes and 10 minutes. In onemethod, the vessel walls are cooled for a period of about 10 minutesbetween about 0 and 10 degrees C. In some methods, cooling is limited intime to the time for which occluding the vessel is permitted. In somemethods, cooling periods are alternated with blood flow periods. In somemethods utilizing perfusion cooling devices, cooling can be performedfor longer periods because blood flow is allowed during the coolingprocess.

In use, cooling devices according to the present invention can also beused to cool an area to the point of freezing tissue, for the purpose ofablating tissue to treat arrhythmias. Sites for such treatments includethe inner walls of the heart chambers and the inner wall of a pulmonaryvein.

In some methods, ultra sound is used to monitor the freezing of tissuenear the cooling device. Frozen tissue is more transparent to ultrasoundthan unfrozen tissue, making frozen tissue show up differently than thesurrounding unfrozen tissue. Monitoring the cooling with ultrasound canprovide an indication of when the cooling process has proceeded too far.Applicants believe the freezing of water in cells can be visualizedbefore irreversible damage and cell death has been caused. In mostmethods, fluoroscopy is used to monitor the position of the coolingdevice relative to the lesion to properly position the cooling devicedistal region. In one method, the temperature of the balloon wall ismeasured with an external temperature probe such as a thin film, device.The temperature of the vessel wall can also be estimated by measuringthe balloon wall temperature, either from the inside or outside of theballoon envelope wall. The temperature of the incoming and outgoingcoolant is measured in some embodiments.

In a preferred method, the pressure inside the cooling device and/orinflatable balloon is measured. Measuring the coolant pressure isparticularly desirable in embodiments where the coolant undergoes aliquid to gas phase change inside of the device. In one method, carbondioxide is used as a coolant and the pressure of the gaseous coolant ismonitored to insure the pressure does not become so high as to stressthe device, and to insure the pressure does not become so low as toallow dry ice formation. Embodiments utilizing liquid carbon dioxide andhaving a return lumen for the gaseous carbon dioxide preferably maintainthe gas pressure above the triple point of carbon dioxide so as toinhibit dry ice formation within the cooling device. Some devicesutilize a high-pressure liquid to low-pressure liquid drop across apressure reducing device such as an orifice. The pressure of the inflowand outflow coolant can be used to monitor the cooling process in thesedevices as well.

Numerous advantages of the invention covered by this document have beenset forth in the foregoing description. It will be understood, however,that this disclosure is, in many respects, only illustrative. Changesmay be made in details, particularly in matters of shape, size, andarrangement of parts without exceeding the scope of the invention. Theinvention's scope is, of course, defined in the language in which theappended claims are expressed.

What is claimed is:
 1. A catheter for delivering treatment fluid into avessel, comprising: a tubular shaft having a distal region; a radiallymovable tube disposed axially with the tubular shaft, the tube having alumen extending therethrough, and a distal delivery port in fluidcommunication with the lumen, wherein the tube may be rotated to pointthe port toward a target area within a vessel; an inflatable balloondisposed near the distal region having an interior in fluidcommunication with the delivery port; an instrument probe having apressure sensor and an ultrasonic device disposed within the interior ofthe balloon, wherein the instrument probe and the tube are independentlymoveable.
 2. The catheter of claim 1, wherein the delivery port isdisposed on a distal tip of the tube and the tube includes a distal bendfor bringing the delivery port near an inner wall of the inflatableballoon.
 3. The catheter of claim 1, wherein the balloon includes anexhaust port for exhausting fluid.
 4. The catheter of claim 1, whereinthe tube is longitudinally movable.
 5. A catheter for deliveringtreatment fluid into a vessel, comprising: a tubular shaft having adistal region; an inflatable balloon disposed near the distal region ofthe tubular shaft; a movable tube disposed axially with the tubularshaft, the tube extending into the balloon, the tube having a lumenextending therethrough, and a distal delivery port in fluidcommunication with the lumen, wherein the tube is rotatable and axiallyslidable relative to the tubular shaft to move the delivery port anddirect treatment fluid through the lumen to various target areas withina vessel, wherein the delivery port is in fluid communication with aninterior of the balloon.
 6. The catheter of claim 5, wherein thedelivery port is disposed on a distal tip of the tube and the tubeincludes a distal bend that brings the delivery port near an inner wallof the inflatable balloon.
 7. The catheter of claim 5, wherein theballoon includes an exhaust port for exhausting fluid.
 8. The catheterof claim 7, wherein the exhaust port comprises an exhaust lumen with apressure valve.
 9. The catheter of claim 5, further comprising apressure sensor disposed within the interior of the balloon.
 10. Thecatheter of claim 9, wherein the pressure sensor is on a stiffening wiredisposed through the balloon.
 11. The catheter of claim 10, furthercomprising a temperature sensor on the stiffening wire.
 12. The catheterof claim 5, further comprising an ultrasonic device on the tube.
 13. Acatheter for delivering treatment fluid into a vessel, comprising: atubular shaft having a distal region; an inflatable balloon disposednear the distal region of the tubular shaft; a movable tube disposedaxially with the tubular shaft, the tube extending into the balloon, thetube having a lumen extending therethrough, and a distal delivery porton a distal tip of the tube, the tube having a distal bend that bringsthe delivery port near an inner wall of the inflatable balloon, whereinthe delivery port is in fluid communication with the lumen, wherein thetube is rotatable and axially slidable within the balloon to move thedelivery port and direct treatment fluid through the lumen to varioustarget areas within a vessel, wherein the delivery port is in fluidcommunication with an interior of the balloon.
 14. The catheter of claim13, further comprising a pressure sensor disposed within the interior ofthe balloon.
 15. The catheter of claim 14, further comprising anultrasonic device disposed within the interior of the balloon.
 16. Thecatheter of claim 15, wherein the pressure sensor and ultrasonic deviceare disposed on an instrument probe.
 17. The catheter of claim 16,wherein the instrument probe and the tube are independently moveable.18. The catheter of claim 13, further comprising a temperature sensordisposed within the interior of the balloon.